Unsuspected Adverse Drug Reactions to Dermatologic Medications: An Epidemiological Hypothesis-Free Screening Study of Real-World Data in Denmark

Global burden of preventable medication-related harm in health care: a systematic review. 1st ed. Geneva: World Health Organization; 2024.

Hazell L, Shakir SAW. Under-reporting of adverse drug reactions. Drug Safety. 2006;12:385–96.

Cornwall JEL, Bygum A, Rasmussen ER. ACE-inhibitor related angioedema is not sufficiently reported to the Danish Adverse Drug Reactions Database. DHPS. 2019;11:105–13. https://doi.org/10.2147/DHPS.S205119.

Article  Google Scholar 

Bate A, Hornbuckle K, Juhaeri J, Motsko SP, Reynolds RF. Hypothesis-free signal detection in healthcare databases: finding its value for pharmacovigilance. Ther Adv Drug Saf. 2019;10:2042098619864744. https://doi.org/10.1177/2042098619864744.

Article  PubMed  PubMed Central  Google Scholar 

Lavertu A, Vora B, Giacomini KM, Altman R, Rensi S. A new era in pharmacovigilance: toward real-world data and digital monitoring. Clin Pharma Therapeutics. 2021;109:1197–202. https://doi.org/10.1002/cpt.2172.

Article  Google Scholar 

Hallas J, Wang SV, Gagne JJ, Schneeweiss S, Pratt N, Pottegård A. Hypothesis-free screening of large administrative databases for unsuspected drug-outcome associations. Eur J Epidemiol. 2018;33:545–55. https://doi.org/10.1007/s10654-018-0386-8.

Article  PubMed  Google Scholar 

Egeberg A, Schwarz P, Harsløf T, Andersen YMF, Pottegård A, Hallas J, et al. Association of potent and very potent topical corticosteroids and the risk of osteoporosis and major osteoporotic fractures. JAMA Dermatol. 2021;157:275–82. https://doi.org/10.1001/jamadermatol.2020.4968.

Article  PubMed  Google Scholar 

Andersen YMF, Egeberg A, Ban L, Gran S, Williams HC, Francis NA, et al. Association between topical corticosteroid use and type 2 diabetes in two European population-based adult cohorts. Diabetes Care. 2019;42:1095–103. https://doi.org/10.2337/dc18-2158.

Article  CAS  PubMed  Google Scholar 

Bots SH, Brown J, Wong AYS, Martin I, Douglas I, Klungel OH, et al. Core concepts: self-controlled designs in pharmacoepidemiology. Pharmacoepidemiol Drug Saf. 2025;34:e70071. https://doi.org/10.1002/pds.70071.

Article  PubMed  PubMed Central  Google Scholar 

Pottegård A, Schmidt SAJ, Wallach-Kildemoes H, Sørensen HT, Hallas J, Schmidt M. Data resource profile: The Danish National Prescription Registry. Int J Epidemiol. 2017;46:798–798f. https://doi.org/10.1093/ije/dyw213.

Article  PubMed  Google Scholar 

Schmidt M, Schmidt SAJ, Sandegaard JL, Ehrenstein V, Pedersen L, Sørensen HT. The Danish National Patient Registry: a review of content, data quality, and research potential. CLEP. 2015. https://doi.org/10.2147/CLEP.S91125.

Article  Google Scholar 

Andersen JS, Olivarius NDF, Krasnik A. The Danish National Health Service Register. Scand J Public Health. 2011;39:34–7. https://doi.org/10.1177/1403494810394718.

Article  PubMed  Google Scholar 

Schmidt M, Pedersen L, Sørensen HT. The Danish Civil Registration System as a tool in epidemiology. Eur J Epidemiol. 2014;29:541–9. https://doi.org/10.1007/s10654-014-9930-3.

Article  PubMed  Google Scholar 

Home. https://english.sundhedsdatastyrelsen.dk/. Accessed 31 Mar 2025

Lai EC-C, Pratt N, Hsieh C-Y, Lin S-J, Pottegård A, Roughead EE, et al. Sequence symmetry analysis in pharmacovigilance and pharmacoepidemiologic studies. Eur J Epidemiol. 2017;32:567–82. https://doi.org/10.1007/s10654-017-0281-8.

Article  PubMed  Google Scholar 

Delvin T, Egsgaard S, Hallas J, Kildegaard H, Lund LC, Rahbek MT. Is the sequence ratio an unbiased estimate of the incidence rate ratio? A simulation study. Pharmacoepidemiol Drug Saf. 2024;33:e5774. https://doi.org/10.1002/pds.5774.

Article  PubMed  Google Scholar 

Hallas J, Pottegård A. Use of self-controlled designs in pharmacoepidemiology. J Intern Med. 2014;275:581–9. https://doi.org/10.1111/joim.12186.

Article  CAS  PubMed  Google Scholar 

Tsiropoulos I, Andersen M, Hallas J. Adverse events with use of antiepileptic drugs: a prescription and event symmetry analysis. Pharmacoepidemiol Drug Saf. 2009;18:483–91. https://doi.org/10.1002/pds.1736.

Article  CAS  PubMed  Google Scholar 

Hallas J. Evidence of depression provoked by cardiovascular medication: a prescription sequence symmetry analysis. Epidemiology. 1996. https://doi.org/10.1097/00001648-199609000-00005.

Article  PubMed  Google Scholar 

Wahab IA, Pratt NL, Wiese MD, Kalisch LM, Roughead EE. The validity of sequence symmetry analysis (SSA) for adverse drug reaction signal detection: SSA FOR ADVERSE DRUG REACTION DETECTION. Pharmacoepidemiol Drug Saf. 2013;22:496–502. https://doi.org/10.1002/pds.3417.

Article  PubMed  Google Scholar 

Sørensen ST, Kristensen FP, Troelsen FS, Schmidt M, Sørensen HT. Health registries as research tools: a review of methodological key issues. Dan Med J. 2023;70:A12220796.

PubMed  Google Scholar 

Lund LC, Hallas J. Recommendations on the calculation of confidence intervals for sequence symmetry analyses. Pharmacoepidemiol Drug Saf. 2023;32:392–4. https://doi.org/10.1002/pds.5578.

Article  PubMed  Google Scholar 

Rahbek MT, Hallas J, Lund LC. Trend adjustment of the sequence difference when performing sequence symmetry analyses. Pharmacoepidemiol Drug Saf. 2024;33:e5723. https://doi.org/10.1002/pds.5723.

Article  PubMed  Google Scholar 

Maclure M. The case-crossover design: a method for studying transient effects on the risk of acute events. Am J Epidemiol. 1991;133:144–53.

Article  CAS  PubMed  Google Scholar 

Greenland S. Confounding and exposure trends in case-crossover and case-time-control designs. Epidemiology. 1996;7:231–9. https://doi.org/10.1097/00001648-199605000-00003.

Article  CAS  PubMed  Google Scholar 

Hallas J, Pottegård A, Wang S, Schneeweiss S, Gagne JJ. Persistent user bias in case-crossover studies in pharmacoepidemiology. Am J Epidemiol. 2016;184:761–9. https://doi.org/10.1093/aje/kww079.

Article  PubMed  Google Scholar 

Thygesen LC, Daasnes C, Thaulow I, Brønnum-Hansen H. Introduction to Danish (nationwide) registers on health and social issues: structure, access, legislation, and archiving. Scand J Public Health. 2011;39:12–6. https://doi.org/10.1177/1403494811399956.

Article  PubMed  Google Scholar 

Aktas H, Bahçe ZŞ. Evaluation of the incidence of anal fissures in patients who systemic isotretinoin therapy for acne. Dermatol Pract Concept. 2023;13:e2023133. https://doi.org/10.5826/dpc.1303a133.

Article  PubMed  PubMed Central  Google Scholar 

Basim P, Yuksel M. A common but not well-known cause in anal fissure development and treatment failure: isotretinoin treatment for acne vulgaris. Med-Science. 2020;9:970. https://doi.org/10.5455/medscience.2020.07.141.

Article  Google Scholar 

Morgan S, Hooper KM, Milne EM, Farquharson C, Stevens C, Staines KA. Azathioprine has a deleterious effect on the bone health of mice with DSS-induced inflammatory bowel disease. IJMS. 2019;20:6085. https://doi.org/10.3390/ijms20236085.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bryer HP, Isserow JA, Armstrong EC, Mann GN, Rucinski B, Buchinsky FJ, et al. AzaThioprine alone is bone sparing and does not alter cyclosporin A-induced osteopenia in the rat. J Bone Miner Res. 1995;10:132–8. https://doi.org/10.1002/jbmr.5650100119.

Article  CAS  PubMed  Google Scholar 

Florén CH, Ahrén B, Bengtsson M, Bartosik J, Obrant K. Bone mineral density in patients with Crohn’s disease during long-term treatment with azathioprine. J Intern Med. 1998;243:123–6. https://doi.org/10.1046/j.1365-2796.1998.00246.x.

Article  PubMed  Google Scholar 

Byrd AL, Belkaid Y, Segre JA. The human skin microbiome. Nat Rev Microbiol. 2018;16:143–55. https://doi.org/10.1038/nrmicro.2017.157.

Article  CAS  PubMed  Google Scholar 

Sales AJ, Joca SRL, Del Bel E, Guimarães FS. The antidepressant-like effect of doxycycline is associated with decreased nitric oxide metabolite levels in the prefrontal cortex. Behav Brain Res. 2024;458:114764. https://doi.org/10.1016/j.bbr.2023.114764.

Article  CAS 

Comments (0)

No login
gif